Salicin from Alangium chinense Ameliorates Rheumatoid Arthritis by Modulating the Nrf2-HO-1-ROS Pathways

Rheumatoid arthritis (RA) is a chronic inflammatory disorder linked to oxidative stress of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). The effects and potential mechanism of salicin on inflammation and oxidative stress of RA-FLSs were examined by MTT, ELISA, and Western blot methods. Salicin significantly reduced cell viability (82.03 +/- 7.06, P < 0.01), cytokines (47.70 +/- 1.48 ng/L for TNF-alpha, 30.03 +/- 3.49 ng/L for IL-6) (P < 0.01), and matrix metalloproteinases-1/-3 expression (P < 0.01) in IL-1/beta-induced RA-FLSs and inhibited ROS generation and p65 phosphorylation (P < 0.01) as compared with IL-1/I-induced treatment. Moreover, salicin promoted Nrf2 nuclear translocation (2.15 +/- 0.21) and HO-1 expression (1.12 +/- 0.05) and reduced ROS production in IL-1/I-induced RA-FLSs (P < 0.01). Salicin not only reduced the collagen-induced arthritis by reducing the clinical score (P < 0.01), inflammatory infiltration, and synovial hyperplasia in vivo but also suppressed the oxidative damage indexes (SOD 155.40 +/- 6.53 U/mg tissue, MDA 152.80 +/- 5.89 nmol/g tissue, GSH 50.98 +/- 3.45 nmol/g tissue, and CAT 0.92 +/- 0.10 U/g protein) (P < 0.01) of ankle joint cells. Conclusively, our findings indicate that salicin ameliorates rheumatoid arthritis, which may be associated with oxidative stress and Nrf2-HO-1-ROS pathways in RA-FLSs